Vortioxetine hydrobromide is a new medicine used for treating adult patients who have major depressive disorder, and developed by Lundbeck pharmaceutical company, the second biggest pharmaceutical manufacturer in Denmark. It is approved by U.S. Food and Drug Administration on Sep. 30, 2013. It has a chemical name of 1-[2-(2,4-dimethylphenylthio)phenyl]piperazine hydrobromide, and a following chemical structure:

Several synthesis routes of Vortioxetine and the derivatives thereof are disclosed in the PCT Publication WO2003029232.
Synthesis route I is shown as follows:

Ortho-fluoronitrobenzene and 2,4-dimethyl thiophenol are used as raw materials to synthesize an intermediate (2,4-dimethylphenyl)(2-nitrophenyl)thioether. Then an intermediate (2,4-dimethylphenyl)(2-aminophenyl)thioether is obtained by catalytic hydrogenating with palladium/carbon. In route 1a, this intermediate is reacted with a mixture of di(2-bromoethyl)amine and di(2-chloroethyl)amine to obtain the final product Vortioxetine. In route 1b, the intermediate (2,4-dimethylphenyl)(2-aminophenyl)thioether is reacted with N-(tert-butoxycarbonyl) iminodiacetic acid to obtain an intermediate 1-tert-butoxycarbonyl-4-[(2,4-dimethylphenylthio)phenyl]-3,5-dioxopiperazine. It is reduced by lithium aluminum hydride or borane to obtain an intermediate 4-tert-butoxycarbonyl-[(2,4-dimethylphenylthio)phenyl]-1-piperazine, which is treated with hydrochloric acid to obtain the final product Vortioxetine.
The synthesis route 2 is shown as follows:

4-tert-butoxycarbonyl-1-piperazine as a raw material is reacted with η6-1,2-dichlorobenzene-η5-cyclopentadienyl iron(II) to obtain 4-({4-[η6-(2-chlorophenyl)η5-cyclopentadienyl iron(II)]-1-tert-butoxycarbonylpiperazine, which is then reacted with 2,4-dimethylthiophenol to obtain an intermediate. The final product Vortioxetine is then obtained by treating the obtained intermediate with hydrochloric acid.
Another synthesis route is disclosed in Journal of Medicinal Chemistry 2011, 54, 3206-3221:

The method for synthesizing the intermediate IIA has been reported in the PCT Publication WO2004067703. That is, the intermediate IIA is obtained by reacting 1,2-dibromo-benzene with 1-tert-butoxycarbonylpiperazine under the catalysis of BINAP and palladium acetate. The synthesis route is shown as follows:

The expensive and specific palladium reagent and phosphine complex are required in the method for synthesizing the intermediate IIA reported in the PCT Publication WO2004067703. The yield is very low, only 52%. Therefore, the method is hard to industrialize, and the cost is very high.
Moreover, according to the prior art, during the process of preparing Vortioxetine, the compound IV is formed by reacting the intermediate IIA with the compound III, then separated, purified and further hydrolyzed to obtain Vortioxetine represented by compound V. However, it should be noted that by adopting this method to prepare Vortioxetine, the yield is not high and an additional separation step is involved, which increases the cost. It is not suitable for industrial production.